Fig. 1: Annotation and curation of candidate LRRK2 pLoF variants.
From: The effect of LRRK2 loss-of-function variants in humans
a, Flow chart showing the variant filtering and curation of candidate LRRK2 LoF variants in the gnomAD, UK Biobank and 23andMe cohorts. Of the 1,103 carriers identified in 23andMe, 749 were confirmed by Sanger sequencing with the remainder untested. b, The ancestry distribution of LRRK2 pLoF variant carriers in gnomAD. AFR, African/African American; AMR, American/Latino; ASJ, Ashkenazi Jewish; EAS, East Asian; FIN, Finnish; NFE, non-Finnish European; SAS, South Asian. The pLoF variants seen more than ten times appear in color with remaining variants in gray. LRRK2 pLoF variants are mostly individually extremely rare (less than 1 in 10,000 carrier frequency), with the exception of two nonsense variants almost exclusively restricted to the admixed AMR population (Cys1313Ter and Arg1725Ter) and two largely NFE-specific variants (Leu2063Ter and Arg772Ter). All variant protein descriptions are with respect to ENSP00000298910.7. c, Schematic of the LRRK2 gene with pLoF variants marked by position, with the height of the marker corresponding to allele count in gnomAD (gray bars) and UK Biobank (blue bars). The 51 exons are shown as rectangles colored by protein ___domain, with the remaining exons in gray. The three variants genotyped in the 23andMe cohort are annotated with their sample count in black text.
